{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:37:16Z","timestamp":1790858236059,"version":"4.1.0"},"reference-count":62,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T00:00:00Z","timestamp":1687305600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100012524","name":"American Lebanese Syrian Associated Charities","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012524","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30 CA021765"],"award-info":[{"award-number":["P30 CA021765"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"name":"St. Jude Cancer Center Support Grant"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,11,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Cerebellar mutism syndrome is a disorder of speech, movement and affect that can occur after tumour removal from the posterior fossa. Projections from the fastigial nuclei to the periaqueductal grey area were recently implicated in its pathogenesis, but the functional consequences of damaging these projections remain poorly understood.<\/jats:p>\n               <jats:p>Here, we examine functional MRI data from patients treated for medulloblastoma to identify functional changes in key brain areas that comprise the motor system for speech, which occur along the timeline of acute speech impairment in cerebellar mutism syndrome. One hundred and twenty-four participants, all with medulloblastoma, contributed to the study: 45 with cerebellar mutism syndrome, 11 patients with severe postoperative deficits other than mutism, and 68 without either (asymptomatic). We first performed a data-driven parcellation to spatially define functional nodes relevant to the cohort that align with brain regions critical for the motor control of speech. We then estimated functional connectivity between these nodes during the initial postoperative imaging sessions to identify functional deficits associated with the acute phase of the disorder. We further analysed how functional connectivity changed over time within a subset of participants that had suitable imaging acquired over the course of recovery. Signal dispersion was also measured in the periaqueductal grey area and red nuclei to estimate activity in midbrain regions considered key targets of the cerebellum with suspected involvement in cerebellar mutism pathogenesis.<\/jats:p>\n               <jats:p>We found evidence of periaqueductal grey dysfunction in the acute phase of the disorder, with abnormal volatility and desynchronization with neocortical language nodes. Functional connectivity with periaqueductal grey was restored in imaging sessions that occurred after speech recovery and was further shown to be increased with left dorsolateral prefrontal cortex. The amygdalae were also broadly hyperconnected with neocortical nodes in the acute phase. Stable connectivity differences between groups were broadly present throughout the cerebrum, and one of the most substantial differences\u2014between Broca\u2019s area and the supplementary motor area\u2014was found to be inversely related to cerebellar outflow pathway damage in the mutism group.<\/jats:p>\n               <jats:p>These results reveal systemic changes in the speech motor system of patients with mutism, centred on limbic areas tasked with the control of phonation. These findings provide further support for the hypothesis that periaqueductal grey dysfunction (following cerebellar surgical injury) contributes to the transient postoperative non-verbal episode commonly observed in cerebellar mutism syndrome but highlights a potential role of intact cerebellocortical projections in chronic features of the disorder.<\/jats:p>","DOI":"10.1093\/brain\/awad209","type":"journal-article","created":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T18:14:02Z","timestamp":1691172842000},"page":"4755-4765","source":"Crossref","is-referenced-by-count":17,"title":["Cerebellar mutism is linked to midbrain volatility and desynchronization from speech cortices"],"prefix":"10.1093","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4121-0592","authenticated-orcid":false,"given":"Samuel S","family":"McAfee","sequence":"first","affiliation":[{"name":"Department of Diagnostic Imaging, St. Jude Children\u2019s Research Hospital , Memphis, TN 38105 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giles","family":"Robinson","sequence":"additional","affiliation":[{"name":"Department of Oncology, St. Jude Children\u2019s Research Hospital , Memphis, TN 38105 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amar","family":"Gajjar","sequence":"additional","affiliation":[{"name":"Department of Oncology, St. Jude Children\u2019s Research Hospital , Memphis, TN 38105 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5336-5650","authenticated-orcid":false,"given":"Silu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Imaging, St. Jude Children\u2019s Research Hospital , Memphis, TN 38105 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asim K","family":"Bag","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Imaging, St. Jude Children\u2019s Research Hospital , Memphis, TN 38105 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darcy","family":"Raches","sequence":"additional","affiliation":[{"name":"Department of Psychology, St. Jude Children\u2019s Research Hospital , Memphis, TN 38105 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather M","family":"Conklin","sequence":"additional","affiliation":[{"name":"Department of Psychology, St. Jude Children\u2019s Research Hospital , Memphis, TN 38105 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raja B","family":"Khan","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Pediatrics, St. Jude Children\u2019s Research Hospital , Memphis, TN 38105 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A","family":"Scoggins","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Imaging, St. Jude Children\u2019s Research Hospital , Memphis, TN 38105 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,6,21]]},"reference":[{"key":"2023110723324593400_awad209-B1","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s00381-010-1328-2","article-title":"Cerebellar mutism: Review of the literature","volume":"27","author":"Gudrunardottir","year":"2011","journal-title":"Childs Nerv Syst"},{"key":"2023110723324593400_awad209-B2","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1093\/neuonc\/noab030","article-title":"Clinical features, neurologic recovery, and risk factors of post-operative posterior fossa syndrome and delayed recovery: A prospective study","volume":"23","author":"Khan","year":"2021","journal-title":"Neuro Oncol"},{"key":"2023110723324593400_awad209-B3","first-page":"444","article-title":"Incidence and severity of postoperative cerebellar mutism syndrome in children with medulloblastoma: A prospective study by the Children\u2019s Oncology Group","volume":"105","author":"Robertson","year":"2006","journal-title":"J Neurosurg"},{"key":"2023110723324593400_awad209-B4","doi-asserted-by":"crossref","first-page":"2186","DOI":"10.1002\/1097-0142(19950415)75:8<2186::AID-CNCR2820750825>3.0.CO;2-F","article-title":"Incidence of cancer in children in the United States. 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